Gene therapy with B-cell maturation antigen/CD3 bispecific antibody encoding plasmid DNA for treating multiple myeloma

Br J Haematol. 2023 May;201(3):417-421. doi: 10.1111/bjh.18230. Epub 2022 May 20.

Abstract

The delivery of bispecific antibodies (BsAbs) targeting B-cell maturation antigen (BCMA) and CD3 using the gene therapy approach is a promising alternative for BsAb administration in patients with multiple myeloma (MM). In the present study, we evaluated the efficacy of this approach using a xenograft model. Tumour growth was significantly delayed in mice treated with single electroporation-enhanced intramuscular injection of plasmid DNA encoding BCMA/CD3 BsAb in contrast to the vehicle control-treated group. Limited toxicity was observed following treatment. This study demonstrates that the gene therapy-based approach for the delivery of BCMA/CD3 BsAb is effective and safe for the treatment of MM.

Keywords: B-cell maturation antigen; bispecific T-cell engager; gene therapy; in vivo electroporation; multiple myeloma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Bispecific* / therapeutic use
  • B-Cell Maturation Antigen / genetics
  • CD3 Complex
  • Humans
  • Mice
  • Multiple Myeloma* / genetics
  • Multiple Myeloma* / therapy
  • Plasmids / genetics
  • T-Lymphocytes

Substances

  • B-Cell Maturation Antigen
  • CD3 Complex
  • Antibodies, Bispecific